Background Unsupervised approaches can be used to analyze complex respiratory and allergic disorders. Objective We investigated the respiratory and allergic phenotypes of children followed in the ...Pollution and Asthma Risk: An Infant Study (PARIS) birth cohort. Methods Information on respiratory and allergic disorders, medical visits, and medications was collected during medical examinations of children at 18 months of age; biomarker data were also collected (total and allergen-specific IgE levels and eosinophilia). Phenotypes were determined by using latent class analysis. Associated risk factors were determined based on answers to questionnaires about environmental exposures. Results Apart from a reference group, which had a low prevalence of respiratory symptoms or allergies (n = 1271 69.4%), 3 phenotypes were identified. On the basis of clinical signs of severity and use of health care resources, we identified a mild phenotype (n = 306 16.7%) characterized by occasional mild wheeze and 2 severe phenotypes separated by atopic status. The atopic severe phenotype (n = 59 3.2%) included 49 (83%) children with wheezing and was characterized by a high prevalence of atopy (61% with allergenic sensitization) and atopic dermatitis (78%). In contrast, atopy was rare among children with the nonatopic severe phenotype (n = 195 11%); this group included 88% of the children with recurrent wheezing. Risk factors for respiratory disease included parental history of asthma, male sex, siblings, day care attendance, exposure to tobacco smoke or molds, indoor renovations, and being overweight, although these factors did not have similar affects on risk for all phenotypes. Conclusion Atopy should be taken into account when assessing the risk of severe exacerbations (that require hospital-based care) in wheezing infants; precautions should be taken against respiratory irritants and molds and to prevent children from becoming overweight.
Few studies have investigated the 24-hour respiratory health effects of personal black carbon (BC) and ultrafine particles (UFP) exposure in schoolchildren. The objective of this study was to ...investigate these associations with the lung function in children 10-years old with and without persistent respiratory symptoms.
We conducted a cross-sectional study in 305 children (147 and 158 with and without persistent respiratory symptoms, respectively) from three European birth-cohorts: PARIS (France) and INMA Sabadell and Valencia (Spain). Personal 24-hour measurements of exposure concentrations to BC and UFP were performed by portable devices, before lung function testing. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the fraction of exhaled nitric oxide (FeNO) were determined.
There was no association of UFP with lung function parameters or FeNO whereas the increase in 24-hour BC exposure concentrations was related to a statistically significant decrease in lung function parameters only among children with persistent respiratory symptoms −96.8 mL (95% Confidence Interval CI: −184.4 to −9.1 mL) in FVC, and −107.2 mL (95% CI: −177.5 to −36.9 mL) in FEV1 for an inter-quartile range of 1160 ng/m3 exposure increase. A significant positive association between BC and FeNO was observed only in children with persistent respiratory symptoms with current wheezing and/or medication to improve breathing FeNO increases with +6.9 ppb (95% CI: 0.7 to 13.1 ppb) with an inter-quartile range BC exposure increase.
Children suffering from persistent respiratory symptoms appear to be more vulnerable to BC exposure.
•Personal 24-hour black carbon exposure was measured in schoolchildren.•Higher black carbon exposure was associated to decreased lung function parameters.•Black carbon exposure was linked to increased FeNO in current symptomatic children.
Little is known about inflammatory pathways of severe recurrent wheeze in preschool children and severe asthma in children.
The aim of the Severe Asthma Molecular Phenotype cohort was to characterize ...phenotypes of severe recurrent wheeze and severe asthma during childhood in terms of triggers (allergic or not), involved cells (eosinophil or neutrophil), and corticoid responsiveness.
Children with moderate-to-severe asthma and preschool children with moderate-to-severe recurrent wheeze were enrolled prospectively. They underwent standardized clinical and blood workup, and bronchoalveolar lavage (BAL) evaluation. Cluster analysis was applied to 350 children with 34 variables.
Three clusters were identified: cluster 1, Neutrophilic steroid-refractory recurrent wheeze phenotype, with 138 children uncontrolled despite high-dose inhaled corticosteroids (ICS) (92%, P < .001), with more history of pneumonia (31%, P < .001), more gastroesophageal reflux disease (37%, P < .001), and the highest blood neutrophil count (mean 4.524 cells/mm
, P = .05); cluster 2, Severe recurrent wheeze with sensitization to a single aeroallergen (12%, P = .002), with 104 children controlled with high-dose ICS (63%, P < .001); cluster 3, Eosinophilic steroid-refractory asthma phenotype, with 108 children uncontrolled despite high-dose ICS (76%, P < .001) with more allergic rhinitis, atopic dermatitis, and food allergies (82%, 40%, 31%, P < .001, respectively). They also had a higher blood eosinophil count and a higher percentage of BAL eosinophil (506/mm
, 2.6%, P < .001 respectively).
Inflammation pathway of asthma and recurrent wheeze are related to eosinophil cells in older children and neutrophil cells in younger children. These results could improve personalized treatments.
To what extent blood granulocyte patterns may predict asthma control remains under-studied. Our aim was to study associations between blood neutrophilia and eosinophilia and asthma control outcomes ...in adults.Analyses were conducted in 474 asthmatics from the first follow-up of the Epidemiological Study on the Genetics and Environment of Asthma (EGEA2), including 242 asthmatics who were adults a decade earlier (EGEA1). At EGEA2, asthma control was assessed using the Global Initiative for Asthma definition (2015), and asthma exacerbations by use of urgent care or courses of oral corticosteroids in the past year. Blood EOS
/EOS
was defined as </≥250 eosinophils·mm
, respectively, and NEU
/NEU
as </≥5000 neutrophils·mm
, respectively. Estimates were adjusted for age, sex and smoking.At EGEA2, NEU
was associated with asthma exacerbations and poor asthma control (OR >2.10). EOS
was associated with higher bronchial hyperresponsiveness (BHR) (OR (95% CI) 2.21 (1.24-3.97)), poor lung function (p=0.02) and higher total IgE level (p=0.002). Almost 50% of asthmatics had a persistent pattern between surveys. Persistent NEU
was associated with poor asthma control at EGEA2 (OR (95% CI) 3.09 (1.18-7.05)). EOS
at EGEA1 and persistent EOS
were associated with higher BHR (OR (95% CI) 2.36 (1.10-5.07) and 3.85 (1.11-13.34), respectively), poor lung function (p<0.06) and higher immunoglobulin E level (p<10
) at EGEA2.Granulocyte patterns were differently associated with asthma outcomes, suggesting specific roles for each one, which could be tested as predictive signatures.
A genomewide association study has shown an association between variants at chromosome 17q21 and an increased risk of asthma. To elucidate the relationship between this locus and disease, we examined ...a large, family-based data set that included extensive phenotypic and environmental data from the Epidemiological Study on the Genetics and Environment of Asthma.
We tested 36 single-nucleotide polymorphisms (SNPs) in the 17q21 region in 1511 subjects from 372 families for an association with asthma. We also tested for genetic heterogeneity according to the age at the onset of asthma and exposure to environmental tobacco smoke in early life.
Eleven SNPs were significantly associated with asthma (P<0.01), of which three (rs8069176, rs2305480, and rs4795400) were strongly associated (P<0.001). Ordered-subset regression analysis led us to select an onset at 4 years of age or younger to classify patients as having early-onset asthma. Association with early-onset asthma was highly significant (P<10(-5) for four SNPs), whereas no association was found with late-onset asthma. With respect to exposure to environmental tobacco smoke in early life, we observed a significant association with early-onset asthma only in exposed subjects (P<5x10(-5) for six SNPs). Under the best-fitting recessive model, homozygous status (GG) at the most strongly associated SNP (rs8069176) conferred an increase in risk by a factor of 2.9, as compared with other genotypes (AG and AA) in the group exposed to environmental tobacco smoke (P=2.8x10(-6); P=0.006 for the test for heterogeneity of the SNP effect on early-onset asthma between groups with tobacco exposure and those without such exposure).
This study shows that the increased risk of asthma conferred by 17q21 genetic variants is restricted to early-onset asthma and that the risk is further increased by early-life exposure to environmental tobacco smoke. These findings provide a greater understanding of the functional role of the 17q21 variants in the pathophysiology of asthma.
Background Whether small-airway obstruction contributes to the long-term evolution of asthma remains unknown. Objectives Our aim was to assess whether the level of forced midexpiratory flow between ...25% and 75% of forced vital capacity (FEF25-75 ) was associated with the persistence of current asthma over 20 years and the subsequent risk for uncontrolled asthma independently of FEV1. Methods We studied 337 participants (142 children and 225 adults) with current asthma (asthma attacks or treatment in the past 12 months) recruited to the Epidemiological Study on the Genetics and Environment of Asthma (EGEA1) and followed up at the 12- and 20-year surveys. Persistent current asthma was defined by current asthma reported at each survey. A lung function test and a methacholine challenge test were performed at EGEA1 and EGEA2. Adjusted odds ratios (ORs) were estimated for FEF25-75 decreased by 10% of predicted value. Results A reduced level of FEF25-75 at EGEA1 increased the risk of long-term asthma persistence (adjusted OR, 1.14; 95% CI, 1.00-1.29). In children the association remained significant after further adjustment for FEV1 and in participants with FEV1 of greater than 80% of predicted value. A reduced FEF25-75 level at EGEA1 was significantly associated with more severe bronchial hyperresponsiveness ( P < .0001) and with current asthma a decade later, with an association that tended to be stronger in those with (adjusted OR, 1.44; 95% CI, 1.14-1.81) compared with those without (adjusted OR, 1.21; 95% CI, 1.05-1.41) asthma exacerbation. Conclusion Our analysis is the first to suggest that small-airway obstruction, as assessed based on FEF25-75 , might contribute to the long-term persistence of asthma and the subsequent risk for poor asthma outcomes independently from effects of the large airways.
Childhood Allergic Asthma Is Not a Single Phenotype Just, Jocelyne, MD, PhD; Saint-Pierre, Philippe, PhD; Gouvis-Echraghi, Rahele, MD ...
The Journal of pediatrics,
04/2014, Letnik:
164, Številka:
4
Journal Article
Recenzirano
Objective IgE-mediated allergic asthma phenotype appears to be heterogeneous. We set out to define distinct allergic phenotypes by unsupervised cluster analysis. Study design A total of 18 variables ...were analyzed: sex and age, eczema and food allergy, asthma duration, asthma severity and control, severe exacerbations, total IgE level, allergic sensitization, fractional exhaled nitric oxide, and functional parameters. Clusters obtained were cross-tabulated with environmental parameters. Results Four clusters were identified in 125 children (average age 8.9 years): (1) 57 children constituted the “House dust mite Sensitization and Mild Asthma” cluster, 98% of these were monosensitized and had mild asthma (74%); (2) 12 children had “Pollen Sensitization with Severe Exacerbations,” 92 % with severe exacerbations and pollen sensitization; (3) 20 children had “Multiple Allergies and Severe Asthma,” with 95% having moderate to severe asthma, and a significantly decreased forced expiratory flow rate at 25%-75% of forced vital capacity, 100% had eczema and higher values of IgE (1123 kU/L) and fractional exhaled nitric oxide (67 ppb) (this cluster was associated with molds at home P = .004); and (4) 36 children had “Multiple Allergic Sensitizations and Mild Asthma,” 97% of these with multiple sensitizations and 100% mild asthma. Conclusions The identification of 2 novel severe allergic asthma phenotypes “Pollen Sensitization with Severe Exacerbations”and “Multiple Allergies and Severe Asthma” could lead to specific targeted treatment.
Atopic dermatitis (AD) is known to predate asthma and other atopic disorders described under the term "atopic march". However, this classic sequence is not always present and only a few studies have ...addressed children at risk of developing asthma. The objective of this study is to define early-onset AD phenotypes leading to asthma.
We performed a cluster analysis with 9 variables of 214 infants with early-onset AD prospectively enrolled in the ORCA cohort and followed each year on the occurrence of asthma until the age of 6.
We identified 3 clusters - cluster 1 (n = 94) with low to no sensitization to food (27.7%) or aeroallergens (10.6%) and moderate AD severity (SCORAD 25.29 +/- 14.6) called "AD with low sensitization"; - cluster 2 (n = 84) characterized by a higher AD severity (SCORAD 32.66+/-16.6) and frequent sensitization to food (98.9%) or aeroallergens (26.2%), most likely multiple (96.4% for food allergens), called "AD with multiple sensitizations" - cluster 3 (n = 36) with parental history, moderate AD severity (SCORAD 24.46+/-15.7), moderate rate of sensitization to food allergens (38.9%) (exclusively single) with no sensitization to aeroallergens, called "AD with familial history of asthma". Percentages of children suffering from asthma at the age of 6 were higher in clusters 2 and 3 (36.1% and 33.3% respectively versus 14.9% in cluster 1, p<0.01).
Two phenotypes in infants with early-onset AD convey a higher risk of developing asthma during childhood: multiple sensitization and familial history of asthma.
The association between air pollution and rhinitis is not well established.
The aim of this longitudinal analysis was to study the association between modeled air pollution at the subjects' home ...addresses and self-reported incidence of rhinitis.
We used data from 1533 adults from two multicentre cohorts' studies (EGEA and ECRHS). Rhinitis incidence was defined as reporting rhinitis at the second follow-up (2011 to 2013) but not at the first follow-up (2000 to 2007). Annual exposure to NO2, PM10 and PM2.5 at the participants' home addresses was estimated using land-use regression models developed by the ESCAPE project for the 2009–2010 period. Incidence rate ratios (IRR) were computed using Poisson regression. Pooled analysis, analyses by city and meta-regression testing for heterogeneity were carried out.
No association between long-term air pollution exposure and incidence of rhinitis was found (adjusted IRR (aIRR) for an increase of 10 μg·m−3 of NO2: 1.00 0.91–1.09, for an increase of 5 μg·m−3 of PM2.5: 0.88 0.73–1.04). Similar results were found in the two-pollutant model (aIRR for an increase of 10 μg·m−3 of NO2: 1.01 0.87–1.17, for an increase of 5 μg·m−3 of PM2.5: 0.87 0.68–1.08). Results differed depending on the city, but no regional pattern emerged for any of the pollutants.
This study did not find any consistent evidence of an association between long-term air pollution and incident rhinitis.
•Rhinitis is an important and prevalent public health issue.•No studies have assessed the effect of outdoor air pollution on rhinitis incidence in adults.•Long-term exposure to NO2, PM10 and PM2.5 was not associated with incident rhinitis.•Our results differed across cities.
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